4-Chlorophenylacetone

[plumbus-nine]

Seen this available at some pretty reputable nootropic vendor under a cryptic abbreviation and w/o the molecular structure so there's a small possibility of me confusing it but the net tells me it's this.
They say it's an 'integrated stress response' inhibitor which reverses the effects of elF2 phosphorylation and inhibits elF2alpha phosphorylation induced stress granule formation. Can anybody translate this to a more plain English?

Edit: Lol, overlooked that they provide some more. Feel free to remove or modify if whatever search engine you're using finds somewhat you don't want - DuckDuckGo doesn't.

Integrated stress response inhibitor. Potently reverses the effects of initiation factor 2α (eIF2α) phosphorylation, IC50=5 nM1. Enhances spatial and fear-associated learning in mice and enhances cognitive function. Mechanism of action involves activation of eiF2β. Suppresses ER stress-induced inflammatory gene expression. Potently attenuates amyloid β-induced neuronal cell death (12.5-25 nM) with no effect on amyloid β production. Reverses hippocampal-dependent cognitive deficits induced by traumatic brain injury in two different injury mouse models.

The integrated stress response (ISR) is a stress response system in that down-regulates protein synthesis and upregulates expression of certain genes, in response to internal or extracellular stresses (for example, hypoxia, low glucose, viral infection, oxidant stress). The result is either the expression of genes to synthesize proteins that fix the damage in the stressed cell, or a cascade of events leading to cellular apoptosis.[1]

EIF-2 protein kinases play an important role in the ISR, as they respond to stress signals by phosphorylating the alpha-subunit of translation initiation factor 2 (eIF2), which modulates gene expression further. In normal cells, eIF2 is an important factor for translation. Phosphorylation of eIF2 converts eIF2 from a substrate to a competitive inhibitor of its nucleotide exchange factor, eIF2B, disrupting protein translation. The phosphorylated eIF2 (P-eIF2) also controls the formation of stress granules (SGs) which play a role in regulating translation of stress effector proteins.

These mechanisms are important for a healthy immune response to protect cells against damage. However, an overactive or malfunctioning ISR has negative consequences and has been linked to neurodegeneration, cognitive disorders, diabetes, and metabolic disorders.[2] Furthermore, the ISR is activated during ageing and contributes to a number of age-related cognitive issues.

ISR inhibitors were hypothesized as being usable to treat ISR-mediated neurodegeneration, but potential candidate compounds were linked to adverse effects due to limiting the effectiveness of the ISR, thus limiting immune response, and rendering the cell incapable of repairing damage.[3] [4]

Doesn't sound too bad but guess it's from rat experiments as usual.

 

[Skorpio]

Great, a p-chloro amphetamine precursor.
Edit: I would really only worry if they seemed to be selling large scale amounts of this. If so I think that is a good sign to avoid mdma for the near future without exhaustively testing it

Also I'd worry about this bit.


"ISR inhibitors were hypothesized as being usable to treat ISR-mediated neurodegeneration, but potential candidate compounds were linked to adverse effects due to limiting the effectiveness of the ISR, thus limiting immune response, and rendering the cell incapable of repairing damage."


Call me conservative, but I would not touch a drug with a novel mechanism of action that hasn't gotten at least to the point of phase I trials.

I think it's a very large risk to be first in man for a mechanism of action (especially for something that is as subtle as a stress response).

 

[plumbus-nine]

Stress response isn't exactly subtle if you got PTSD, social anxiety or similarly disabling issues but I agree with that it's a different thing to take a drug with completely new primary mechanism than some old candidates which were shelved off not to having enough capitalistic potential but were shown to be somewhat safe, even when in animals. But we continue to see medicine pass phase I-III only to wreck some organs when on market. So trials can only statistically minimize danger but not absolutely so, it's always possible to be one of the few exceptions.

Blocking the body's stress response (if we understand the same under this pretty nonspecific term) by dissociatives gave me a new impression on life. First I thought it'd change me just to experience that I was capable of being relaxed while among strangers but then it became addictive and with addiction the dissos turned against me. If this compound would offer a similar nothing-really-is-worth-to-be-afraid-of feeling then I'd take the risk. Yeah, noticed the similarity to a para-chloro PEA but it lacks the amine, so are you pretty sure that it's a precursor?

And if, how much does the dosage matter, is p-Cl amph toxicity something like paracetamol overdose activity where you're mostly safe unless crossing a certain threshold or is it direct toxicity a la this PPT+ (forgot its name) which kills dopaminergic neurons? Just know that p-Cl amph's are used to kill serotonergic neurons which certainly I don't want but NMDA is one of the more potent neurotoxins around e.g. but it's only dangerous when too much of it acts in the same time.

But yeah when it's just like e.g. propranolol which keeps your heart from racing wildly then it's not worth the risk, even when I like propranolol, it's too subtle and too much tiredness inducing in higher dosages. Taking the tiredness and decrease in physical metabolism away would be a first step. I mean, the fact that beta blockers bring my heart from 105+ down to 70 indicate that there's still a lot of stress related stuff going on, doesn't it?

 

[Skorpio]

Stress response isn't exactly subtle if you got PTSD, social anxiety or similarly disabling issues but I agree with that it's a different thing to take a drug with completely new primary mechanism than some old candidates which were shelved off not to having enough capitalistic potential but were shown to be somewhat safe, even when in animals. But we continue to see medicine pass phase I-III only to wreck some organs when on market. So trials can only statistically minimize danger but not absolutely so, it's always possible to be one of the few exceptions.

Blocking the body's stress response (if we understand the same under this pretty nonspecific term) by dissociatives gave me a new impression on life. First I thought it'd change me just to experience that I was capable of being relaxed while among strangers but then it became addictive and with addiction the dissos turned against me. If this compound would offer a similar nothing-really-is-worth-to-be-afraid-of feeling then I'd take the risk. Yeah, noticed the similarity to a para-chloro PEA but it lacks the amine, so are you pretty sure that it's a precursor?

And if, how much does the dosage matter, is p-Cl amph toxicity something like paracetamol overdose activity where you're mostly safe unless crossing a certain threshold or is it direct toxicity a la this PPT+ (forgot its name) which kills dopaminergic neurons? Just know that p-Cl amph's are used to kill serotonergic neurons which certainly I don't want but NMDA is one of the more potent neurotoxins around e.g. but it's only dangerous when too much of it acts in the same time.

But yeah when it's just like e.g. propranolol which keeps your heart from racing wildly then it's not worth the risk, even when I like propranolol, it's too subtle and too much tiredness inducing in higher dosages. Taking the tiredness and decrease in physical metabolism away would be a first step. I mean, the fact that beta blockers bring my heart from 105+ down to 70 indicate that there's still a lot of stress related stuff going on, doesn't it?

I don't think this is related to the response to stressful situations at all (as mediated short term by adrenaline and longer term by cortisol).

The integrated stress response refers to ER (endoplasmic reticulum) stress, which can come in the form of too many unfolded proteins, oxidative stress, osmotic stress and others. These are sub cellular (often sub-organellar) processes that are really important for maintenance of proper cellular function (impaired er stress response often is involved in the etiology of neurodegenerative conditions, and cancers often can be dealt with by fucking with stress responses).

 

[Tryptamite]

It could be reacted with ammonia/methylamine to give 4-Cl(meth)amphetamine.

No idea as a drug in itself.

 

[plumbus-nine]

It could be reacted with ammonia/methylamine to give 4-Cl(meth)amphetamine.

Interesting, maybe they sell it as a precursor but fuck 4-Cl meth is a selective neurotoxin.

 

[Tryptamite]

Yeah. 4- subbed amps are pretty dodgy in general.
I think 4-CA was used as an anti depressant once, or trialed at least.